Molecular dynamics (MD) simulations are employed to study the structure and function of the
protein bacteriorhodopsin (bR), a 26 kD protein which residues in the purple membrane of the
bacterium Halobacterium halobium. Bacteriorhodopsin undergoes a light-driven cyclic process,
which pumps protons across the membrane, in order to maintain a proton gradient necessary for
ATP synthesis. The cycle is initiated through a trans --+ cis isomerization of the chromophore
retinal, which is bound to a lysine residue via a protonated Schiff base linkage. The study of bR
is facilitated through development of the program VMD for visualization of the simulation results,
and the program NAMD for MD calculations on parallel computers. Initially, MD simulations
are used to develop a refined three-dimensional structure of the protein, using the experimentally
determined electron-microscopy structure of bRas a basis, and to determine equilibrium positions
for several water molecules within the protein interior. MD simulations are then used to model the
early isomerization reaction events in the bR photocycle, for both the native (wild-type) system
and several bR mutants. The simulations reveal the possibility for bR to form two or three unique
photoproducts, distinguished by the retinal isomeric state and the orientation of the Schiff base
proton relative to nearby water molecules and negatively charged aspartic acids. One particular
photoproduct is suggested to lead to successful proton pump activity, while the remaining structures
return back to the initial state; this result is supported by simulations of non-functional bR mutants,
which do not exhibit formation of the suggested functional photoproduct. The very fast initial
retinal photoexcitation and subsequent isomerization reaction are also examined in detail using a
combined quantum/ classical simulation technique, in which the evolution of the density matrix for
the retinal isomerization degree of freedom is computed using the Liouville-von Neumann equation.
The simulations result in wild-type bR exhibiting a non-adiabatic crossing between excited states
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after 500 fs, while the computed excited-state lifetimes for mutants D85N and D212N are an order
of magnitude longer. The results compare well with recent femtosecond spectroscopy data for these
systems and demonstrate that the lifetime of the excited state is controlled by the position and
slope of the first potential energy surface crossing point.